The mechanisms of determinant-specific Ir gene control and of antigen recognition by T and B lymphocytes were explored at several levels in the response to myoglobin. In a secondary in vitro antibody response, Ir gene control was manifested by a failure of (high responder x low responder) F1 T cells to help low responder B cells, even though the latter could be helped by carrier-specific T cells and so must have been present and competent. This result was independent of macrophage source. Low responder T cells, from mice neonatally tolerant to high responder Ia antigens, were competent to help high but not low responder B cells, and so were phenotypically identical to F1 or high responder T cells. B cell restriction correlated with Lyb5- phenotype. The response to horse myoglobin was controlled by an unusual gene in H-2D. Monoclonal antibodies specific for topographic determinants of myoglobin are being sequenced and crystallization of their Fab fragments with myoglobin is being attempted. B cell presentation of antigen is under study. T cell lines specific for myoglobin have been prepared and are being cloned.